WO1997012035A3 - Animaux transgeniques pour xenotransplantation avec limitation du rejet induit par des anticorps - Google Patents

Animaux transgeniques pour xenotransplantation avec limitation du rejet induit par des anticorps Download PDF

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Publication number
WO1997012035A3
WO1997012035A3 PCT/US1996/015255 US9615255W WO9712035A3 WO 1997012035 A3 WO1997012035 A3 WO 1997012035A3 US 9615255 W US9615255 W US 9615255W WO 9712035 A3 WO9712035 A3 WO 9712035A3
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WO
WIPO (PCT)
Prior art keywords
transgenic animals
cells
antibody
organs
tissues
Prior art date
Application number
PCT/US1996/015255
Other languages
English (en)
Other versions
WO1997012035A2 (fr
Inventor
Lisa E Diamond
John S Logan
Geurard W Byrne
Ajay Sharma
Original Assignee
Nextran
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nextran filed Critical Nextran
Priority to EP96932320A priority Critical patent/EP0853665A2/fr
Priority to BR9610843A priority patent/BR9610843A/pt
Priority to MXPA98002434A priority patent/MXPA98002434A/es
Priority to AU71170/96A priority patent/AU727546B2/en
Priority to JP51354297A priority patent/JP2001517924A/ja
Priority to IL12379196A priority patent/IL123791A0/xx
Publication of WO1997012035A2 publication Critical patent/WO1997012035A2/fr
Publication of WO1997012035A3 publication Critical patent/WO1997012035A3/fr

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1048—Glycosyltransferases (2.4)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/108—Swine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/02—Animal zootechnically ameliorated
    • A01K2267/025—Animal producing cells or organs for transplantation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Animal Husbandry (AREA)
  • Cell Biology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Toxicology (AREA)
  • Transplantation (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Procédé de xénotransplantation d'organes, de tissus, de cellules ou d'éléments non viables, ce qui limite ou empêche des rejets provoqués par des anticorps, y compris un rejet hyperaigu. Ce procédé consiste à préparer des animaux transgéniques exprimant au moins une enzyme masquant ou diminuant le niveau du déterminant antigénique de Galα(1,3)Gal et au moins un inhibiteur de complément, tel que CD59, DAF et/ou MCP. Ces animaux transgéniques exprimant à la fois une enzyme de diminution du déterminant antigénique de gal et un inhibiteur de complément posséderont des niveaux masqués ou diminués du déterminant antigénique de gal et seront beaucoup moins susceptibles de produire un rejet provoqué par des anticorps après la transplantation, et l'expression de l'inhibiteur de complément supprimera également l'activation du complément et limitera encore plus un risque de réaction immune grave après la transplantation d'organes, de tissus, de cellules et d'éléments non viables provenant de ces animaux transgéniques. De plus, l'invention concerne des animaux transgéniques exprimant une pluralité d'inhibiteurs de complément ou d'autres protéines provenant d'un locus de gènes au niveau d'un seul site d'intégration. L'invention présente des avantages résidant dans la production d'organes, de tissus, de cellules et d'éléments non viables xénogènes qui peuvent être transplantés efficacement et sans risques à l'homme et présentent une capacité de limitation ou d'élimination d'un rejet provoqué par des anticorps beaucoup plus importante qu'il n'était possible d'obtenir jusqu'à maintenant, ce qui diminuera considérablement la nécessité d'obtenir des organes, des tissus, des cellules ou des éléments non viables à partir de l'homme ou du primate.
PCT/US1996/015255 1995-09-27 1996-09-23 Animaux transgeniques pour xenotransplantation avec limitation du rejet induit par des anticorps WO1997012035A2 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP96932320A EP0853665A2 (fr) 1995-09-27 1996-09-23 Animaux transgeniques pour xenotransplantation avec limitation du rejet induit par des anticorps
BR9610843A BR9610843A (pt) 1995-09-27 1996-09-23 Animais transgênicos para xenotransplante com reduzida rejeição mediada por anticorpo
MXPA98002434A MXPA98002434A (es) 1995-09-27 1996-09-23 Animales transgenicos para xenotrasplante con rechazo reducido de anticuerpos mediados.
AU71170/96A AU727546B2 (en) 1995-09-27 1996-09-23 Transgenic animals for xenotransplantation with reduced antibody-mediated rejection
JP51354297A JP2001517924A (ja) 1995-09-27 1996-09-23 抗体媒介性拒絶反応を低減させた異種移植のためのトランスジェニック動物
IL12379196A IL123791A0 (en) 1995-09-27 1996-09-23 Transgenic animals for xenotransplantation with reduced antibody-mediated rejection

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US446195P 1995-09-27 1995-09-27
US60/004,461 1995-09-27
US08/675,773 US6166288A (en) 1995-09-27 1996-07-03 Method of producing transgenic animals for xenotransplantation expressing both an enzyme masking or reducing the level of the gal epitope and a complement inhibitor
US08/675,773 1996-07-03

Publications (2)

Publication Number Publication Date
WO1997012035A2 WO1997012035A2 (fr) 1997-04-03
WO1997012035A3 true WO1997012035A3 (fr) 1997-06-12

Family

ID=26673032

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/015255 WO1997012035A2 (fr) 1995-09-27 1996-09-23 Animaux transgeniques pour xenotransplantation avec limitation du rejet induit par des anticorps

Country Status (10)

Country Link
US (1) US6166288A (fr)
EP (1) EP0853665A2 (fr)
JP (1) JP2001517924A (fr)
CN (1) CN1278299A (fr)
AU (1) AU727546B2 (fr)
BR (1) BR9610843A (fr)
CA (1) CA2233040A1 (fr)
IL (1) IL123791A0 (fr)
MX (1) MXPA98002434A (fr)
WO (1) WO1997012035A2 (fr)

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WO1997012035A2 (fr) 1997-04-03
EP0853665A2 (fr) 1998-07-22
US6166288A (en) 2000-12-26
BR9610843A (pt) 1999-07-13
AU727546B2 (en) 2000-12-14
CN1278299A (zh) 2000-12-27
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